This application for renewal of the University of Virginia Cancer Center Support Grant builds on its original strengths in basic science research. However, it has been substantially re-structured to enhance the cohesiveness and cancer focus of the individual Programs and to facilitate meaningful interactions between laboratory and clinical scientists. The Cancer Center Support Grant has been organized into five Programs: Program 1, Cell Signaling focuses on molecular mechanisms of intracellular regulation including oncogenes, receptors, intracellular signal transduction, gene regulation and DNA replication, which are key to understanding normal and malignant growth. Program 2, Endocrinology focuses on growth, differentiation and regulation of endocrine cells, particularly of the pituitary, thyroid and gonads. This Program has a distinguished record of clinical, translational and fundamental research. Program 3, Immunology has great strengths in the areas of immune cell activation, antigen presentation/recognition and auto-immunity, issues which are of fundamental and practical importance in cancer immunology. Program 4, Metastasis, Invasion and Cell Surfaces is a new Program, built on existing basic science strengths in membranes, extracellular matrices and proteases, which will be brought to bear on the important problems of tumor invasion and metastasis. Program 5, Clinical Oncology is a new Program designed to provide the clinical venue for interactions with the four laboratory-based Programs. Its goal is to identify cellular or immunologic targets for therapy or diagnosis; develop drugs or biologicals to attack that target; and test these drugs or biologicals in the clinical setting. Inter-disciplinary working groups with individuals drawn from each stage of the development process are being established to facilitate this process. In addition to the Programmatic re-structuring, the Cancer Center has consolidated its inpatient and ambulatory cancer care facilities, established a centralized clinical trials protocol review and monitoring system, coordinated oncology research programs with existing areas of related research strength and initiated the recruitment of clinical and translational oncology researchers. The net result of these changes is expected to be a system which enhances understanding of cancer and facilitates scientific improvements in cancer treatment, diagnosis and prevention.